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ser - protein. Coenzyme A. Pantothenate. 2-mercaptoethylamine. ADP. Acyl carrier protein. Fritz Lipmann. Noble prize for Chemistry 1953 (shared with Sir Hans Krebs). "for his discovery of co-enzyme A and its importance for intermediary metabolism". 1899-1986. Pyruvate dehydrogenase.

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Presentation Transcript
slide1

ser - protein

Coenzyme A

Pantothenate

2-mercaptoethylamine

ADP

Acyl carrier protein

slide2

Fritz Lipmann

Noble prize for Chemistry 1953 (shared with Sir Hans Krebs)

"for his discovery of co-enzyme A and its importance for intermediary metabolism"

1899-1986

slide5

Pyruvate dehydrogenase

The core of the complex consists of 60 copies of E2.

At the periphery of the complex are:

  • 30 copies of E1 (itself a tetramer with subunits a2b2)
  • 12 copies of E3 (a homodimer), plus 12 copies of an

E3 binding protein that links E3 to E2.

slide6

Pyruvate dehydrogenase

OH

OH

O

+

+

+

1.

CO2

E1

TPP

TPP-CH

TPP-CH

H+

H3C-C-COO-

CH3

CH3

O

O

S – C –CH3

S – C –CH3

2.

+

E2

E2

+ H+

E2

E2

E2

E2

O

E2

+

3.

+

CoA-SH

CoA-S -

C –CH3

Acetyl CoA

+

FAD

FADH2

FADH2

E3-

E3-

E3-

+

4.

FAD

E3-

S

S

SH

SH

S

SH

S

SH

SH

SH

+

5.

+

NADH + H+

NAD

slide7

1. Inhibited by AcCoA and NADH

  • AcCoA (competes with CoA for E2),
  • NADH (competes with NAD for E3)

2. Regulated by phosphorylation

E2 is associated with PDH kinase and

PDH phosphatase which act on E1

·phosphorylation of the E1 subunit inhibits

·dephosphorylation activates.

·Phosphorylation controled by NADH/NAD,

AcCoA/CoA and ATP/ADP.

Increasing these ratios promotes phosphorylation and

hence decreases activity.

THEREFORE: Phosphorylation of E1 increases and activity

of PDH decreases when energy charge is high.

·Pyruvate inhibits PDH kinase in the presence of high [ADP]

and therefore promotes dephosphorylation and

increase in activity.

·In muscle high [Ca2+] activates phosphatase. At onset

of exercise [Ca2+], pyruvate and ADP increase resulting

in increased PDH phosphatase (Ca) and decrease PDH

kinase due to increased pyruvate + ADP, and decreased

ATP/ADP ratio.

Regulation of PDH:

slide8

Sir Hans Krebs

Noble Prize for Chemistry

"for his discovery of the citric acid cycle"

1900 - 1981

slide10

COO-

SCoA

O C

COO-

C O

C H

COO-

C H2

CH3

COO-

HO CH

HO C COO-

HC H

C H2

COO-

COO-

COO-

COO-

C H2

H C

H C COO-

C H

C H

HO

COO-

COO-

COO-

COO-

C H2

COO-

C H2

C H2

C H2

COO-

H C H

COO-

H C H

O C

C O

COO-

C O

C H

COO-

COO-

C H2

SCoA

COO-

HO CH

HO C COO-

HC H

C H2

COO-

COO-

COO-

COO-

C H2

COO-

H C

H C COO-

O C

COO-

C H

C H

HO

C H

COO-

C H2

COO-

COO-

COO-

HO CH

HO C COO-

HC H

C H2

COO-

COO-

COO-

COO-

C H2

COO-

C H2

C H2

C H2

COO-

H C H

COO-

H C H

COO-

C O

C H2

C O

H C

COO-

H C COO-

SCoA

C H

C H

HO

COO-

COO-

COO-

COO-

C H2

COO-

C H2

C H2

C H2

H C H

COO-

H C H

C O

C O

COO-

SCoA

Make a couple of copies of this for class

slide11

O

C

O-

Biotin

+ CO2